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Prostate Cancer MetastaticPhase 2TAXYNERGYNCT01718353

Early Switch From First-Line Docetaxel/Prednisone to Cabazitaxel/Prednisone and the Opposite Sequence, Exploring Molecular Markers in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

A Phase 2 study testing DOCETAXEL (XRP6976), CABAZITAXEL (XRP6258) and Prednisone in people with Prostate Cancer Metastatic, run by Sanofi at 19 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Docetaxel and cabazitaxel are cancer chemotherapy agents of the taxane drug class. The purpose of this study is to explore the benefit, for treatment of metastatic castration-resistant prostate cancer (mCRPC), of a regimen in which participants begin treatment with either of these two taxane drugs (docetaxel or… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer Metastatic
What is being tested?
DOCETAXEL (XRP6976), CABAZITAXEL (XRP6258) and Prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
63 participants
Where
19 sitesin 2 countries
Study dates
Mar 2013to Aug 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically- or cytologically-confirmed prostate adenocarcinoma with documented distant metastases (M1 disease).
  • Progressive disease while receiving hormonal therapy or after surgical castration.
  • Effective castration (serum testosterone levels ≤50 ng/dL) by orchiectomy and/or luteinizing hormone releasing hormone agonists or antagonist with or without anti-androgens.

Who cannot join

  • Prior chemotherapy for prostate cancer, except estramustine and adjuvant/neoadjuvant treatment completed >3 years ago. Prior treatment with sipuleucel-T immunotherapy was allowed at the condition participant did not receive prior chemotherapy.
  • Less than 28 days elapsed from prior treatment with estramustine, radiotherapy or surgery to the time of random allocation.
  • Prior beta isotope therapy, whole pelvic radiotherapy, or radiotherapy to >30% of bone marrow.
  • Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03) at the time of random allocation.
  • Less than 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status >2.
Show all 22Show fewer
  • History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
  • Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa and pT1) bladder cancer were allowed, as well as any other cancer for which chemotherapy had been completed ≥3 years ago and from which the participant had been disease-free for ≥3 years.
  • Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to random allocation.
  • Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack.
  • Any of the following within 3 months prior to random allocation: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.
  • Acquired immunodeficiency syndrome (AIDS)-related illnesses or known HIV disease requiring antiretroviral treatment.
  • Any severe acute or chronic medical condition which could impair the ability of the participant to participate in to the study or interfere with interpretation of study results, or participant unable to comply with the study procedures.
  • Concomitant treatment with biphosphonates or denosumab except if the dose had been stable for 4 weeks prior to enrollment.
  • Absence of signed and dated Institutional Review Board (IRB)-approved participant informed consent prior to enrollment into the study.
  • Participants with reproductive potential who did not agree to use an accepted and effective method of contraception during the study treatment period. The definition of "effective method of contraception" was based on the investigator's judgment.
  • History of hypersensitivity to docetaxel or polysorbate 80.
  • Inadequate organ and bone marrow function.
  • Contraindications to the use of corticosteroid treatment.
  • Symptomatic peripheral neuropathy grade >2 (NCI CTCAE v.4.03).
  • Treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a two-week wash-out period was necessary for participants who were already on these treatments).
  • The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial locations and contacts

19 sites in 2 countries.

19 sites in 2 countries

United States14 sites

  • Investigational Site Number 840002

    Baltimore, Maryland, 21230

  • Investigational Site Number 840007

    Bethesda, Maryland, 20817

  • Investigational Site Number 840003

    Birmingham, Alabama, 35294-3300

  • Investigational Site Number 840009

    Charleston, South Carolina, 29414

  • Investigational Site Number 840010

    Cherry Hill, New Jersey, 08003

  • Investigational Site Number 840015

    East Orange, New Jersey, 07018

  • Investigational Site Number 840005

    Indianapolis, Indiana, 46202

  • Investigational Site Number 840004

    Madison, Wisconsin, 53705

  • Investigational Site Number 840025

    Metairie, Louisiana, 70006

  • Investigational Site Number 840001

    New York, New York, 10021

  • Investigational Site Number 840013

    New York, New York, 10029-6574

  • Investigational Site Number 840017

    Rockville, Maryland, 20850

  • Investigational Site Number 840012

    Seattle, Washington, 98109

  • Investigational Site Number 840102

    Washington D.C., District of Columbia, 20016-2695

Other trials in United States

Canada5 sites

  • Investigational Site Number 124001

    Edmonton, Alberta, T6G 1Z2

  • Investigational Site Number 124004

    Montreal, Quebec, H2L 4M1

  • Investigational Site Number 124002

    Montreal, Quebec, H2W1S6

  • Investigational Site Number 124006

    Québec, Quebec, G1R 2J6

  • Investigational Site Number 124005

    Sherbrooke, Quebec, J1H 5N4

Other trials in Canada

About this study

Official title: Phase II Trial to Evaluate Benefit of Early Switch From First-Line Docetaxel/Prednisone to Cabazitaxel/Prednisone and the Opposite Sequence, Exploring Molecular Markers and Mechanisms of Taxane Resistance in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Have Not Received Prior Chemotherapy

Docetaxel and cabazitaxel are cancer chemotherapy agents of the taxane drug class. The purpose of this study is to explore the benefit, for treatment of metastatic castration-resistant prostate cancer (mCRPC), of a regimen in which participants begin treatment with either of these two taxane drugs (docetaxel or cabazitaxel, in combination with prednisone) and are switched to the other taxane drug if prostate-specific antigen (PSA) value does not decrease ≥30% after 4 cycles. As defined in study protocol amendment 3, efficacy results are summarized for all participants combined, irrespective of which agent (docetaxel or cabazitaxel) was administered initially, rather than separately for the two groups based on taxane administered initially. One of the primary outcome measures is percentage of participants with a ≥50% sustained decrease from baseline in PSA at any time during the trial. By providing an opportunity for patients to switch taxane based on early PSA response, there may be a difference in result for this measure versus result in a study where it was not possible to switch. The other primary outcome measures are change from baseline in circulating tumor cells (CTCs) biomarkers percent androgen receptor nuclear localization (%ARNL) and microtubule bundling (MTB).

Read the detailed description
  • Participants were treated until progressive disease, unacceptable toxicity, death, or participant's refusal of further study treatment. All participants were followed until death or the study cut-off date, whichever came first.
  • Study cut-off was 1 month after the last participant last treatment.
  • Participants alive at the cut-off date were not followed for overall survival.
Being tested
DOCETAXEL (XRP6976), CABAZITAXEL (XRP6258), Prednisone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DOCETAXEL (XRP6976)Drug

    Also called Taxotere®

    Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous

  • CABAZITAXEL (XRP6258)Drug

    Also called Jevtana®

    Pharmaceutical form: Concentrate and solvent for solution for infusion Route of administration: Intravenous

  • PrednisoneDrug

    Pharmaceutical form: Tablet Route of administration: Oral

Study groups in NCT01718353
Study groupRoleWhat they receive
Docetaxel + Prednisone (Treatment A)ExperimentalDocetaxel 75 mg/m^2 intravenous (IV) infusion on Day 1 of Cycle 1 and every 3 weeks (q3w) thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4 switched to Cabazitaxel 25mg/m^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.
Receives: Drug: DOCETAXEL (XRP6976); Drug: Prednisone
Cabazitaxel + Prednisone (Treatment B)ExperimentalCabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4 switched to Docetaxel 75mg/m^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.
Receives: Drug: CABAZITAXEL (XRP6258); Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With PSA Response

    PSA response was defined as ≥50% decrease in PSA levels in both treatment arms from baseline, during the whole treatment, before treatment switch and after treatment switch. PSA progression was defined as decline of PSA from baseline (an increase of ≥25% [at least 2ng/ml] over the nadir value, confirmed by a second PSA value at least 3 weeks apart) and no decline of PSA from baseline (an increase of ≥25% [at least 2ng/ml] over the baseline value after 12 weeks of treatment, confirmed by a second PSA value at least 3 weeks apart). Because the purpose of this study is to explore the benefit of a regimen in which participants are switched to a different taxane if PSA does not decrease ≥30% after 4 cycles, irrespective of which agent (docetaxel or cabazitaxel) is administered initially, the data for participants who began treatment with docetaxel and for those who began treatment with cabazitaxel were combined for the efficacy analyses.

    Measured: Baseline, Pre-dose every 3 weeks, 30 days after last treatment administration (End of treatment [EOT]), every 3 months (for 1 year) then every 6 months until PSA progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks)

  2. Drug-target Engagement in Circulating Tumor Cells (CTCs): Change From Baseline at Cycle 1 Day 8 in Percent Androgen Receptor Nuclear Localization (%ARNL) by Categories of PSA Decrease From Baseline (≥50%, Not ≥50%) After Cycle 4

    Analysis of CTCs is a co-primary endpoint. Growth of prostate cancer cells is dependent on sustained androgen receptor (AR) nuclear signaling. Taxanes (e.g., docetaxel and cabazitaxel) may mediate some of their activity in prostate cancer by impairing AR trafficking along the microtubules from the tumor cell cytoplasm into the nucleus, as a result of taxane-induced microtubule bundling (MTB). Blood samples were collected at baseline and post-treatment to allow isolation of CTCs, which were evaluated for tumor cell biomarker measures %ARNL and MTB score. %ARNL was assessed by quantitative analysis of images of CTCs captured by geometrically enhanced differential immunocapture (GEDI). Reduction from baseline in %ARNL (percentage of total cellular AR that is located in the nucleus) may indicate inhibition of AR signaling. Change from baseline in %ARNL at Cycle 1 Day 8 is summarized by categories of participants with PSA decrease from baseline (≥50%, Not ≥50%) after Cycle 4.

    Measured: Baseline and Cycle 1 Day 8, Cycle 4

  3. Drug-target Engagement in CTCs: Change From Baseline at Cycle 1 Day 8 in MTB by Categories of PSA Decrease From Baseline (≥30%, Not ≥30%) After Cycle 4

    Analysis of CTCs is a co-primary endpoint. Growth of prostate cancer cells is dependent on sustained AR nuclear signaling. Taxanes (e.g., docetaxel and cabazitaxel) may mediate some of their activity in prostate cancer by impairing AR trafficking along the microtubules from the tumor cell cytoplasm into the nucleus, as a result of taxane-induced MTB. Blood samples were collected at baseline and post-treatment to allow isolation of CTCs, which were evaluated for tumor cell biomarker measures %ARNL and MTB score. MTB in images of CTCs captured by GEDI was qualitatively assessed by three independent operators for increase compared with baseline on a scale of 0 to 3 from no to most MTB increase. Increase from baseline in MTB may indicate inhibition of AR signaling. Change from baseline in MTB at Cycle 1 Day 8 is summarized by categories of participants with PSA decrease from baseline (≥30%, Not ≥30%) after Cycle 4.

    Measured: Baseline and Cycle 1 Day 8, Cycle 4

Secondary outcomes (7)

  1. Progression Free Survival (PFS)

    PFS was defined as the time interval between the date of random allocation of the treatment and the date of first documentation of any of the following: radiographic tumor progression (using Modified Response Evaluation Criteria in Solid Tumors [RECIST1.1] before any switch and during the study), clinical progression (including skeletal-related events, increasing pain requiring escalation of narcotic analgesics, urinary obstruction), PSA progression or death from any cause. Analysis was performed by Kaplan Meier method.

    Measured: From Baseline until DP or death due to any cause or study cut off, whichever was earlier (Maximum duration: 60 weeks)

  2. PSA Progression Free Survival

    PSA progression-free survival before any switch and PSA progression free survival during the study was defined as the time interval between the date of Day 1 of Cycle 1 to the date of either first PSA progression or death due to any cause whichever came first. PSA progression was defined as decline of PSA from baseline (an increase of ≥25% [at least 2ng/mL] over the nadir value, confirmed by a second PSA value at least 3 weeks apart) and no decline of PSA from baseline (an increase of ≥25% [at least 2ng/mL] over the baseline value after 12 weeks of treatment, confirmed by a second PSA value at least 3 weeks apart).

    Measured: From Baseline until DP or death due to any cause or study cut off date, whichever was earlier (Maximum duration: 60 weeks)

  3. Percentage of Participants With Objective Response

    Measured: From baseline until DP or study cut off, whichever was earlier (Maximum duration: 60 weeks)

  4. Radiographic Progression-free Survival (rPFS)

    Measured: From baseline, every 12 weeks until radiological tumor progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks)

  5. Clinical Progression-free Survival (cPFS)

    cPFS was assessed before switch and during the study including skeletal-related events (SRE), increasing pain requiring escalation of narcotic analgesics, urinary obstruction, etc. SRE included pathological fractures and/or spinal cord compression, need for bone irradiation (including radioisotopes or bone surgery), change of antineoplastic therapy (including introduction of bisphosphonates or denosumab in the face of increase in pain) to treat bone pain. Pain was assessed using present pain intensity (PPI) scale (0=no pain, up to 5=excruciating pain) and analgesics used for cancer pain (1 point for non-narcotic medications and 4 points for narcotic medications).

    Measured: Baseline, Pre-dose every 3 weeks, EOT, every 3 months (for 1 year) until first SRE occurrence or death or study cut-off, whichever was earlier (Maximum duration: 60 weeks)

  6. Overall Survival

    Overall survival before switch and overall survival during the study was defined as the time interval from the date of random allocation to the date of death due to any cause until study cut-off date.

    Measured: From baseline until death due to any cause or study cut-off, whichever was earlier (Maximum duration: 60 weeks)

  7. Percentage of Participants With ≥30% and ≥50% Reduction in PSA Response

    Participants with ≥30% and ≥50% reduction in PSA response from base line were evaluated in participants who were previously treated with a high potency androgen receptor (AR)-targeted agent (AR signaling inhibitor or cytochrome P450 17 alphahydroxylase/17,20lyase [CYP 17] inhibitor).

    Measured: From baseline until DP or study cut-off, whichever was earlier (Maximum duration: 60 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2012 (estimated)
  2. Study startMar 2013
  3. Primary completionAug 2015
  4. Study completionAug 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
63 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01718353
Sponsor's protocol ID
CABAZL06056
Other IDs
U1111-1130-9893
Acronym
TAXYNERGY
Status last verified
Aug 2016
First submitted
29 Oct 2012
Last updated
20 Nov 2017
Data monitoring committee
No

Publications

  • Tagawa ST, Antonarakis ES, Gjyrezi A, Galletti G, Kim S, Worroll D, Stewart J, Zaher A, Szatrowski TP, Ballman KV, Kita K, Tasaki S, Bai Y, Portella L, Kirby BJ, Saad F, Eisenberger MA, Nanus DM, Giannakakou P. Expression of AR-V7 and ARv567es in Circulating Tumor Cells Correlates with Outcomes to Taxane Therapy in Men with Metastatic Prostate Cancer Treated in TAXYNERGY. Clin Cancer Res. 2019 Mar 15;25(6):1880-1888. doi: 10.1158/1078-0432.CCR-18-0320. Epub 2018 Oct 9.

    PubMed 30301829

  • Antonarakis ES, Tagawa ST, Galletti G, Worroll D, Ballman K, Vanhuyse M, Sonpavde G, North S, Albany C, Tsao CK, Stewart J, Zaher A, Szatrowski T, Zhou W, Gjyrezi A, Tasaki S, Portella L, Bai Y, Lannin TB, Suri S, Gruber CN, Pratt ED, Kirby BJ, Eisenberger MA, Nanus DM, Saad F, Giannakakou P; TAXYNERGY Investigators. Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naive, Metastatic, Castration-Resistant Prostate Cancer. J Clin Oncol. 2017 Oct 1;35(28):3181-3188. doi: 10.1200/JCO.2017.72.4138. Epub 2017 Jun 20.

    PubMed 28632486

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DOCETAXEL (XRP6976), CABAZITAXEL (XRP6258) and Prednisone in people with Prostate Cancer Metastatic, run by Sanofi at 19 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With PSA Response (time frame: Baseline, Pre-dose every 3 weeks, 30 days after last treatment administration (End of treatment [EOT]), every 3 months (for 1 year) then every 6 months until PSA progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01718353, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2017.

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